**3. Conclusions**

To date the hydrophobic region AGAAAAGA palindrome (113-120) of the unstructured Nterminal region (1-123) of prions has little existing experimental structural data available. This Chapter successfully constructs three molecular structure models for AGAAAAGA palindrome (113-120) by using some suitable template 3NHD.pdb from Protein Data Bank and refinement of the Models with several optimization techniques within AMBER 11. These models should be very helpful for the experimental studies of the hydrophobic region AGAAAAGA palindrome of prion proteins (113-120) when the NMR or X-ray molecular structure of prion AGAAAAGA peptide has not been easily determined yet. These constructed Models for amyloid fibrils may be useful for the goals of medicinal chemistry.

This Chapter also introduces numerous practical computational approaches to construct the molecular models when it is difficult to obtain atomic-resolution structures of proteins with traditional experimental methods of X-ray and NMR etc, due to the unstable, noncrystalline and insoluble nature of these proteins. Known structures can be perfectly reproduced by these computational methods, which can be compared with contemporary methods. As we all know, X-ray crystallography finds the X-ray final structure of a protein, which usually need refinements using a SA protocol in order to produce a better structure. SA is a global search procedure and usually it is better to hybrid with local search procedures. Thus, the computational methods introduced in this Chapter should be better than SA along to refine X-ray final structures.
